Medroxyprogesterone acetate (Depo-Provera) is a progestin-containing contraceptive medicine that inhibits pituitary gonadotropins. It also inhibits endometrial cell proliferation and may be used to treat abnormal uterine bleeding.

Medroxyprogesterone acetate (Depo-Provera) Uses:

• Abnormal uterine bleeding:

  • When there is no organic pathology present, such as fibroids or uterine cancer, to treat irregular bleeding brought on by hormone imbalance.

• Amenorrhea, secondary (tablet):

  • If there is abnormal uterine bleeding, it can be used to treat the condition even in the absence of biological diseases such as fibroids or uterine cancer.

• Contraception (104 mg/0.65 mL and 150 mg/mL injection):

  • can use as a contraceptive.

• Endometrial hyperplasia prevention (tablet):

  • Endometrial hyperplasia prevention in non-hysterectomized postmenopausal women using 0.625 mg of oral conjugated estrogens daily.
  • Note: When progesterone is required, micronized progesterone is preferable over medroxyprogesterone acetate due to safety concerns.

• Endometrial carcinoma (400 mg/mL injection) (100 mg tablet [Canadian product]):

  • Endometrial cancer that is inoperable, recurring, and/or metastatic may be treated with it supplementary therapy or palliative care.

• Endometriosis (104 mg/0.65 mL injection):

  • To manage the pain of endometriosis.

• Off-Label Use of Medroxyprogesterone in Adults:

  • Abnormal uterine bleeding
  • Endometrial hyperplasia (treatment)
  • Hot flashes (intramuscular administration)
  • Paraphilia/hypersexuality (treatment)

---

Medroxyprogesterone acetate (Depo-Provera) Dose in Adults:

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of abnormal uterine bleeding:

• Oral: Starting on days 16 to 21 of the menstrual cycle, take 5 or 10 mg every day for 5 to 10 days.
• When appropriately primed with endogenous or exogenous oestrogen, a proposed dose of 10 mg daily for 10 days beginning on day 16 of the cycle causes the best secretory change of the endometrium.
• After stopping the use of medroxyprogesterone, withdrawal bleeding may happen within 3 to 7 days.
• Patients with a history of recurrent bouts of abnormal uterine bleeding may benefit from planned menstrual cycles.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of acute Abnormal uterine bleeding, (off-label):

• Oral: 20 mg three times a day for 7 days.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of secondary Amenorrhea:

• 5 to 10 mg orally, taken daily for 5 to 10 days.
• You can begin therapy at any time.
• When the endometrium has been sufficiently primed with either endogenous or exogenous oestrogen, a dose of 10 mg taken daily for 10 days causes the endometrium to convert optimally.
• Within 3 to 7 days following discontinuation, bleeding may happen.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Contraception:

• Depo-Provera Contraceptive:
  • IM: 150 mg every 3 months (every 13 weeks)
• Depo-subQ Provera 104:
  • SubQ: 104 mg every 3 months (every 12 to 14 weeks)

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of recurrent or metastatic endometrial carcinoma (adjunctive/ palliative treatment):

• IM (Depo-Provera): Initial: 400 to 1,000 mg/week
• Oral (100 mg tablet [Canadian product]):
  • Manufacturer’s labeling:
    • Usual dose: 200 to 400 mg daily.
    • Doses >200 mg daily may not confer additional benefit.
    • If the condition gets better or the disease stabilises, 200 mg per day can be enough to keep things going.
    • If there is no improvement after three months, stop the therapy.

Medroxyprogesterone acetate (Depo-Provera) Dose as an alternative agent in the treatment of Endometrial hyperplasia prevention in postmenopausal persons receiving daily conjugated estrogen:

• Oral: Starting on day 1 or day 16 of the cycle, take 5 or 10 mg every day for 12 to 14 days straight.
• Use for the shortest time at the lowest effective dose consistent with treatment objectives when treating postmenopausal patients.
• To determine whether treatment is still required, reevaluate the patients.
• Patients who have undergone a hysterectomy typically do not require a progestin; treatment is recommended for postmenopausal women with a uterus to lower the risk of endometrial cancer.
• When progesterone is required, micronized progesterone is preferable over medroxyprogesterone acetate due to safety concerns.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Endometrial hyperplasia (off-label):

Note: It is unknown how long therapy should last.

• Atypical endometrial hyperplasia or endometrial intraepithelial neoplasia:

  • Oral: For 12 to 14 days each month, take 10 to 20 mg once daily (continuous dose) or 10 to 20 mg once daily (cyclic dosing).

• Non-atypical hyperplasia:

  • Oral: For 10 to 12 days per cycle, take 10 mg once daily (continuous dosage) or 10 mg once daily (cyclic dosing); continuous daily oral dosing produces better outcomes than cyclic daily oral dosing.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Endometriosis (Depo-subQ Provera 104):

• SubQ: 104 mg every 3 months (every 12 to 14 weeks)

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Hot flashes (off-label):

• IM: 400 mg as a single dose.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Paraphilia/hypersexuality (off-label):

• Males (Note: Avoid its use if active pituitary pathology, hepatic failure, or thromboembolic disease):
  • IM (Depo-Provera):
    • 100 to 600 mg weekly
  • Oral:
    • 100 to 500 mg per day

---

Medroxyprogesterone acetate (Depo-Provera) Dose in Children:

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of abnormal uterine bleeding:

• Adolescents:

  • Oral: Commencing on day 16 or day 21 of the menstrual cycle, 5 to 10 mg for 5 to 10 days.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Amenorrhea:

• Adolescents:

  • Oral: 5 to 10 mg per day for 5 to 10 days.

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Contraception:

• Adolescents:

  • If the patient is not breastfeeding, the initial dose should be administered only during the first five days of a regular menstrual cycle, within five days of delivery if she is, or only at the sixth postpartum week if she is pregnant. 
  • IM (Depo-Provera):
    • 150 mg every 3 months (every 13 weeks)
  • SubQ (depo-subQ Provera 104):
    • 104 mg every 3 months (every 12 to 14 weeks)

Medroxyprogesterone acetate (Depo-Provera) Dose in the treatment of Endometriosis-associated pain:

• Adolescents:

  • SubQ (depo-subQ Provera 104):
    • 104 mg every 3 months; treatment longer than 2 years is not recommended because it may affect bone mineral density.

---

Medroxyprogesterone acetate Pregnancy Category: X

• Many products are not advised for use as a pregnancy test or by pregnant women who are suspected of being pregnant.
• If you use injectable medroxyprogesterone (MPA) contraception during pregnancy, there is no increased risk of birth abnormalities.
• When MPA is given during the first trimester, male newborns have been shown to have hypospadias, and female babies have been found to have clitoral hypertrophy or labial fusion.
• MPA contraceptive injection may cause ectopic pregnancy.
• Fertility can be impaired by high doses
• [US Boxed Warning] Unless other methods of birth control are inadequate
• It is not recommended to use medroxyprogesterone contraceptives as a long-term method of birth control (ie for more than 2 years).
• The median time it takes to have a baby or return to ovulation after discontinuing MPA contraceptive injections is 10 months. This is independent of the length of the use.

Medroxyprogesterone acetate use during breastfeeding:

• Breast milk contains medroxyprogesterone (MPA).
• After maternal administration of 150 mg/mL of depot medroxyprogesterone acetate to 10 women, the concentrations of MPA were reported.
• The administration took place 6 to 7 weeks after delivery; maternal plasma and milk were collected over 12 weeks.
• There was a large variation in plasma and MPA milk concentrations between women, as well as within the same woman at different sampling points.
• The highest milk concentrations were observed within two weeks of injection. They also decreased over time.
• Most samples had milk concentrations lower than the maternal plasma.
• After maternal DMPA IM administration, MPA metabolites weren't detected in breastfed male infants' urine.
• Additionally, the urine concentrations in breastfed male infants were not significantly different from those not exposed to MPA through breast milk.
• There are no negative consequences for behavioural development or for the composition, quality, quantity, or composition of breast milk.
• MPA tablet use is not advised for nursing moms by the manufacturers.
• Contrary to popular belief, guidelines allow the use of injectable MPA contraceptives.
• The manufacturer recommends that medroxyprogesterone 400mg/mL not be used by lactating women.

---

Dose in Kidney Disease:

 

Medroxyprogesterone acetate (Depo-Provera) Dose in Liver disease:

• Medroxyprogesterone is extensively metabolized in the liver and elimination is significantly reduced in patients with advanced hepatic disease.
• Most products are contraindicated in patients with hepatic impairment.
• If needed for the palliative treatment of metastatic endometrial carcinoma, monitor closely; withhold or discontinue treatment if liver dysfunction develops and do not resume until the liver function has returned to normal.

---

Common Side Effects of Medroxyprogesterone acetate (Depo-Provera):

• Central nervous system:

  • Headache
  • Nervousness

• Endocrine & metabolic:

  • Amenorrhea
  • Weight gain
  • Menstrual disease

• Gastrointestinal:

  • Abdominal pain

Less Common Side Effects of Medroxyprogesterone acetate (Depo-Provera):

• Cardiovascular:

  • Edema

• Central Nervous System:

  • Dizziness
  • Anxiety
  • Depression
  • Insomnia
  • Irritability
  • Fatigue

• Dermatologic:

  • Acne Vulgaris
  • Alopecia
  • Skin Rash

• Endocrine & Metabolic:

  • Decreased Libido
  • Change In Menstrual Flow
  • Hypermenorrhea
  • Hot Flash

• Gastrointestinal:

  • Abdominal Distension
  • Diarrhea
  • Nausea
  • Bloating

• Genitourinary:

  • Abnormal Pap Smear
  • Bacterial Vaginosis
  • Breast Tenderness
  • Dysmenorrhea
  • Mastalgia
  • Urinary Tract Infection
  • Uterine Hemorrhage
  • Vaginal Hemorrhage
  • Vaginitis
  • Vulvovaginal Candidiasis
  • Leukorrhea

• Infection:

  • Influenza

• Local:

  • Pain At Injection Site
  • Atrophy At Injection Site
  • Induration At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Limb Pain
  • Leg Cramps
  • Weakness

• Respiratory:

  • Bronchitis
  • Nasopharyngitis
  • Pharyngitis
  • Sinusitis
  • Upper Respiratory Tract Infection

Frequency of Side effects Not Defined:

• Central Nervous System:

  • Euphoria
  • Malaise

• Endocrine & Metabolic:

  • Cushing Syndrome
  • Hypercalcemia
  • Lipodystrophy

• Genitourinary:

  • Breakthrough Bleeding
  • Spotting

• Local:

  • Injection Site Nodule
  • Tenderness At the Injection Site

---

Contraindications to Medroxyprogesterone acetate (Depo-Provera):

Injection (104 mg/0.65 mL):

• Allergy or sensitivity to medroxyprogesterone
• Active thrombophlebitis
• thromboembolic conditions (current or past)
• Cerebral vascular disease
• Undiagnosed vaginal bleeding
• Breast cancer (known, suspected or history of);
• Hepatic disease is a serious problem.
• pregnancy

Injection (150 mg/mL):

• Hypersensitivity to medroxyprogesterone and any component of the formulation
• Active thrombophlebitis
• Thromboembolic disorders (current and/or past) or cerebral Vascular Disease;
• Undiagnosed vaginal bleeding
• Breast cancer (known, suspected or history of);
• Hepatic disease is a serious problem.
• pregnancy;
• Diagnostic test for pregnancy

Injection (400 mg/mL):

• Hypersensitivity to medroxyprogesterone and any component of the formulation
• Active thrombophlebitis
• thromboembolic conditions (current or past)
• Cerebral vascular disease

Tablet

• Angioedema or angioedema due to medroxyprogesterone
• DVT or PE (current and/or historical);
• Active or past history of arterial embombolic disease (eg stroke, MI)
• estrogen- or progesterone-dependent tumour (known or suspected) (excludes 100 mg tablet [Canadian product] indicated for endometrial cancer);
• Undiagnosed abnormal Genital Bleeding;
• Breast cancer (known, suspected or history of);
• Hepatic impairment or disease; pregnant

Canadian labelling: Additional contraindications not in the US labelling

Injection (50 mg/mL, 104 mg per 0.65 mL, 150 mg/mL):

• History or current malignant or benign liver tumours
• Current or past migraines with focal aura
• Any ocular lesion that results from ophthalmic vessel disease.
• Undiagnosed breast pathology
• Progestin-dependent Neoplasia known or suspected;
• Myocardial Infarction (current or historical)
• Urinary tract bleeding
• The presence of multiple risk factors, including severe or multiple risk factors, for arterial or vein thrombosis.
  • severe hypertension (persistent bp >=160/100 mm Hg);
  • hereditary or acquired predisposition for venous or arterial thrombosis (eg, Factor V Leiden and Prothrombin G20210 A mutation, activated protein C (APC) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant);
  • severe dyslipoproteinemia;
  • Heavy smoking (>15 cigarettes per day) or older than 35 years.
  • Diabetes mellitus and vascular involvement

Tablet

• Vascular disease can cause vision loss, partial or total.

Warnings and precautions

• Suppression of the adrenals:

  • Potentially suppresses the hypothalamic-pituitary-adrenal (HPA) axis, which lowers plasma cortisol levels, cortisol secretion levels, and plasma ACTH levels.
  • There can be cushingoid symptoms.

• Anaphylaxis/hypersensitivity reactions:

  • Anaphylaxis and anaphylactoid reactions have been reported after injections; immediate access should be made to medication for hypersensitivity reactions.

• Loss of bone mineral density: [US Boxed Warn]

  • Bone mineral density may decline if medroxyprogesterone contraceptive injections are used for an extended period of time (BMD).
  • It is unclear if it will lower peak bone mass or make osteoporotic fractures more likely to occur later in life.
  • The duration of drug use is a factor in the loss. It may not be fully reversible upon discontinuation.
  • In making treatment decisions, it is important to weigh the impact on adolescents' peak bone mass against the possibility of unintended pregnancies.
  • Patients with a high risk of osteoporosis should think about different forms of birth control (eg, metabolic bone disease, chronic alcohol or tobacco use, anorexia, strong family history, osteoporosis-related medication use, anticonvulsants, corticosteroids, and other methods of contraception).
  • Patients should get adequate amounts of c Vitamin D, and calcium.
  • For long-term endometrial carcinoma, it is worth assessing the bone mineral density of patients who have been given high doses of medroxyprogesterone.

• [US Boxed Warning] Breast Cancer

  • Data from the Women's Health Initiative (WHI), shows that postmenopausal women who use conjugated estrogens (CE), in combination with medroxyprogesterone (MPA) showed an increased risk of developing invasive breast cancer.
  • This risk decreases when therapy is stopped.
  • According to the WHO study, women who underwent hysterectomy with CE did not have a higher risk of developing breast cancer.
    Women who had used depo-medroxyprogesterone in the previous five years, and for longer durations, had a greater chance of developing breast cancer (12 months or more).
  • As a result of their oestrogen or progestin doses, the timing of therapy commencement, length of therapy, mode of administration, and patient characteristics, postmenopausal women undergoing hormone therapy may be more likely to develop breast cancer.
  • Increased breast density may be associated with hormone therapy.
  • An increase in abnormal mammogram findings needs further investigation.
  • Breast cancer patients may experience severe hypercalcemia from estrogen use. If this happens, discontinue estrogen use.
  • Many products are not recommended for patients with breast cancer.
  • Women with breast cancer, or suspected breast cancer, should not use medroxyprogesterone to treat endometrial carcinoma.

• Dementia: [US Boxed Warning]

  • Using estrogens alone or in combination with progestin is not recommended for preventing dementia.
  • Women over 65 with CE and MPA showed an increase in probable dementia, according to the Women's Health Initiative Memory Study (WHIMS).
  • The WHI memory studies were performed on women aged >=65 years. It is not known if the findings can be applied to younger postmenopausal females.
  • For the treatment or prevention of cognitive decline or dementia at any age, hormone therapy is not advised.

• Ectopic pregnancy

  • Patients with severe abdominal pain should be aware that contraception can lead to ectopic pregnancy.

• Endometrial cancer:

  • After taking conjugated estrogens, MPA is used to lower the risk of endometrial hyperplasia in female patients who do not have a hysterectomy.
  • Endometrial cancer is more likely to occur in women who use unopposed estrogen.
  • To lower the risk of endometrial Hyperplasia, a precursor to endometrial cancer, progestin may be added to oestrogen therapy.
  • It is crucial to carry out the proper diagnostic procedures, including endometrial sampling, if required, in order to rule out cancer in women who have undetected irregular vaginal blood flow.
  • In comparison to synthetic estrogens with identical oestrogen dosages, there is no evidence to imply that natural estrogens have a different risk profile.
  • The risk of developing endometrial cancer seems to depend on the type of therapy administered and can endure even after it is stopped.
  • A progestin should not be used if low doses are being administered locally to treat vaginal atrophy. However, there are insufficient long-term data (>1 years) to support this recommendation.

• Hypertriglyceridemia:

  • Triglycerides may rise in women on oestrogen plus progesterone therapy if they already have hypertriglyceridemia; stop if pancreatitis develops.

• Ovarian cancer:

  • There is conflicting information on the relationship between the risk of ovarian cancer and the use of estrogen/progestin treatment or menopausal oestrogen.
  • An association may exist, but the risk of developing a serious condition is unlikely. The duration of therapy can also influence the likelihood of developing a severe reaction.

• Retinal vascular embolism:

  • In cases of sudden vision loss, proptosis, diplopia or migraine, discontinue treatment pending further examination.
  • If retinal vascular or papilledema is found on examination, discontinue treatment permanently

• Vaginal bleeding

  • Bleeding or spotting can occur.
  • If you notice persistent, irregular vaginal bleeding after regular periods, it is worth having your endometrial sample taken to rule out malignancy.

• Weight loss

  • After two years, medroxyprogesterone-based contraception frequently causes a weight gain of about 3.7 kg.

• Abnormal uterine bleeding:

  • For abnormal uterine bleeding (AUB) caused by ovulatory dysfunction (not caused by structural factors), whether chronic or acute, a specific treatment should be taken into account.
  • Likewise, take medical restrictions on the treatments that are offered into account. Think about if pregnancy or contraception are needed concurrently.

• Asthma

  • Patients with asthma should be cautious when using estrogen plus progestin therapy. This could worsen the condition.

• Cardiovascular disease: [US-Boxed Warning]

  • To prevent cardiovascular disease, estrogens with progestin shouldn't be used.
  • According to data from the Women's Health Initiative (WHI) research, postmenopausal ladies aged 50 to 79 who use CE 0.625 mg with MPA 2.5 mg had an increased risk of stroke, pulmonary emboli (PE), deep vein thrombosis, and pulmonary emboli (DVT).
  • Additional risk factors include systemic lupus erythematosus, hypertension, hypercholesterolemia, diabetes mellitus, obesity, smoking, and/or a history of venous thromboembolism (VTE).
  • You should manage your risk factors well. If you experience adverse cardiovascular events, stop using the product immediately.
  • It may not be safe to use in females with active deep vein thrombosis (DVT), pulmonary embolism (PE), arterial thromboembolic illnesses (stroke and MI), and a history of such conditions.
  • Patients with cardiovascular disease risk factors should be cautious when using contraception.
  • If you experience thrombosis while using contraception, stop taking it (unless there is another acceptable contraceptive option).

• Depression

  • Patients with a history or depression should be cautious.

• Diabetes:

  • Progestin therapy plus estrogen may cause glucose tolerance problems; women with diabetes should be cautious.

• Fluid retention can lead to more severe diseases

  • Patients with fluid retention-related diseases, such as cardiac or renal dysfunction, should be cautious.

• Epilepsy:

  • Patients with epilepsy should be cautious about using estrogen plus progestin therapy. This could worsen the condition.

• Hepatic dysfunction

  • Patients with impaired liver function are unable to metabolize progestins and estrogens.
  • If you have ever used oestrogen or been pregnant, you should exercise caution if you have a history of cholestatic jaundice.
  • Stop using if jaundice appears or if there is acute or chronic liver dysfunction.
  • Many products are not recommended for people with hepatic impairment.
  • Women with severe liver dysfunction should not use medroxyprogesterone to treat endometrial cancer. If this happens, it is best to stop using the medication.

• Hepatic hemomangiomas

  • Patients with hepatic hemorhagic hemangiomas should be cautious about using estrogen plus progestin therapy. This could worsen the condition.

• Hypoparathyroidism:

  • Hypoparathyroidism patients should be cautious about using estrogen plus progestin therapy; it is possible to develop estrogen-induced hypocalcemia.

• Migraine

  • Patients suffering from migraine should be careful. It may worsen the condition.

• Porphyria

  • Patients with porphyria should be treated with estrogen plus progestin therapy. This may worsen the condition.

• Systemic lupus, erythematosus

  • Patients with systemic Lupus Erythematosus (SLE) should be cautious about using estrogen plus progestin therapy. This could worsen the condition.

Medroxyprogesterone acetate: Drug Interaction

Risk Factor C (Monitor therapy)
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
C1 inhibitors	Progestins may enhance the thrombogenic effect of C1 inhibitors.
Choline C 11	Antiandrogens may lessen Choline C 11's therapeutic impact.
CYP3A4 Inducers (Moderate)	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
CYP3A4 Inhibitors (Strong)	May raise the level of medroxyPROGESTERone in the serum. Atazanavir, Cobicistat, Darunavir, Lopinavir, Nelfinavir, and Saquinavir are exceptions.
Deferasirox	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Elexacaftor	Hormonal contraceptives may intensify Elexacaftor's negative or hazardous effects. In particular, there may be an elevated risk for rash.
Erdafitinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Flibanserin	Flibanserin's serum levels may rise in response to progestins (contraceptive).
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca)	Could make progestins' harmful or hazardous effects worse.
LamoTRIgine	May decrease the serum concentration of Progestins (Contraceptive).
Metreleptin	May lower the level of progestins in the serum (Contraceptive).
Nalmefene	The serum concentration of progestins may rise in response to metreleptin (Contraceptive).
Pegloticase	The serum content of nalmefene may rise when medroxyPROGESTERone is present.
Pegvaliase	Could make PEGylated Drug Products' therapeutic impact less effective. MedroxyPROGESTERONE may intensify Pegvaliase's harmful or hazardous effects. Particularly, there may be an elevated risk of anaphylaxis or hypersensitivity responses.
Sarilumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Selegiline	Progestins (Contraceptive) may increase the serum concentration of Selegiline.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Thalidomide	Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Triazolam	The serum levels of triazolam may rise after using hormonal contraceptives.
Voriconazole	May raise progesterone levels in the blood (Contraceptive). The serum levels of voriconazole may rise in response to progestins (contraceptive).
Risk Factor D (Consider therapy modification)
Acitretin	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Progestin-only preparations shouldn't be depended upon because they may not be effective at preventing pregnancy while using acitretin. During acitretin therapy, alternative, nonhormonal methods of contraception must be used.
Anticoagulants	Anticoagulants' therapeutic effects may be lessened by progestins. More particular, some progestins and progestin-estrogen combos may have prothrombotic actions that work against any anticoagulant effects. Management: Carefully balance the progestins' possible advantages against their potential increased risk of thromboembolism and procoagulant effects. Under some conditions, use is deemed contraindicated. For particular advice, consult the relevant policies.
Aprepitant	May lower the level of progestins in the serum (Contraceptive). Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant.
Artemether	May lower the level of progestins in the serum (Contraceptive). Management: All women of reproductive potential who are taking artemether should think about utilising an alternative method of contraception (i.e., one that is not hormonal).
Atazanavir	May raise progesterone levels in the blood (Contraceptive). Atazanavir, however, may result in lower ethinyl estradiol levels and reduced efficiency of oral contraceptive medications. Management: When using combination estrogen/progestin medications, take into account an extra means of contraception. It is possible to utilise depot medroxyprogesterone acetate without the use of supplementary contraception.
Barbiturates	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.
Bexarotene (Systemic)	May lower the level of progestins in the serum (Contraceptive). Management: Women who are sexually active and on bexarotene should utilise two trustworthy methods of contraception (including at least one nonhormonal form).
Bile Acid Sequestrants	May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives containing progestin at least one to four hours before or six to eight hours after taking a bile acid sequestrant.
Bosentan	May lower the level of progestins in the serum (Contraceptive). Management: Do not solely rely on hormonal contraceptives for all women of reproductive potential who are taking bosentan; instead, use an alternative (i.e., non-hormonal) method of contraception.
Brigatinib	May lower the level of progestins in the serum (Contraceptive). Management: For at least 4 months following the last dosage of brigatinib, females of reproductive potential should use an alternative, non-hormonal method of contraception.
CarBAMazepine	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.
Carfilzomib	Could make progestins' thrombogenic impact stronger (Contraceptive). In patients who need carfilzomib medication, alternate, non-hormonal methods of contraception should be taken into account.
Cenobamate	Could lower the blood level of hormonal contraceptives. Management: While taking cenobamate, women should utilise additional or substitute non-hormonal birth control.
Cladribine	May reduce the hormonal contraceptives' therapeutic effect. Management: During cladribine dosage and for at least 4 weeks after the final dose in each treatment period, women who are using systemically acting hormonal contraceptives should add a barrier device.
CloBAZam	May lower the level of progestins in the serum (Contraceptive).
Cobicistat	May raise progesterone levels in the blood (Contraceptive). When treating patients who are taking cobicistat-containing medications, take into account an alternative, nonhormone-based method of contraception. Atazanavir and cobicistat are specifically contraindicated with dronabinol.
CYP3A4 Inducers (Strong)	May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Dabrafenib	May lower the level of progestins in the serum (Contraceptive). Treatment: Women who are sexually active or who are planning a pregnancy should take contraception that is highly effective, non-hormonal, and alternative for at least 2 weeks (if taking dabrafenib alone) or 4 months (if taking dabrafenib plus trametinib).
Darunavir	May decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception.
Efavirenz	May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.
Enzalutamide	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.
Eslicarbazepine	May lower the level of progestins in the serum (Contraceptive). Management: For women who are capable of having children, alternative, non-hormonal methods of birth control should be taken into account.
Felbamate	May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of contraception.
Fosamprenavir	The serum concentrations of the active metabolite(s) of fosamprenavir may drop when using progestins (contraceptives). Fosamprenavir may lower the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. There is no requirement for supplemental contraception when using injected depot medroxyprogesterone acetate.
Fosaprepitant	May lower the level of progestins in the serum (Contraceptive). Probably the active metabolite aprepitant is the cause of this effect. Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant.
Fosphenytoin	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.
Ivosidenib	May lower the level of progestins in the serum (Contraceptive). Treatment: If a patient is taking ivosidenib, consider non-hormonal contraception alternatives.
Lesinurad	May lower the level of progestins in the serum (Contraceptive). Treatment: Patients on lesinurad who want reliable contraception are advised to use an additional nonhormonal method of contraception.
Lixisenatide	May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives 11 hours or more after giving lixisenatide, whichever comes first.
Lopinavir	May lower the level of progestins in the serum (Contraceptive). Lopinavir may raise the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. Without the need for supplementary contraception, injectable depot medroxyprogesterone acetate and etonogestrel implants may be utilised.
Lorlatinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.
Lumacaftor	May lower the level of progestins in the serum (Contraceptive). Management: If lumacaftor and ivacaftor are taken together, avoid using hormone-based contraceptives; instead, choose an other, non-hormonal type of contraception.
MiFEPRIStone	May reduce the progestins' therapeutic impact (Contraceptive). MiFEPRIStone may raise the level of progestins in the serum (Contraceptive). Management: During and for four weeks after mifepristone treatment, women of reproductive potential should use an efficient, nonhormonal method of contraception.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Mycophenolate	May lower the level of progestins in the serum (Contraceptive). Management: Employing a different (nonhormonal) type of contraception should be taken into consideration.
Nelfinavir	May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.
Oxcarbazepine	May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use a second or additional nonhormonal method of contraception.
Perampanel	May lower the level of progestins in the serum (Contraceptive). Treatment: Patients should utilise an alternative method of contraception that is not hormonally based both while taking perampanel and for one month after stopping it.
Phenytoin	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.
Pitolisant	Could lower the blood level of hormonal contraceptives. Treatment: Patients who use hormonal contraception should be urged to continue using a non-hormonal mode of contraception for at least 21 days following the cessation of pitolisant therapy.
Pomalidomide	Pomalidomide's thrombogenic action may be strengthened by progestins. Care should be taken while using hormone replacement treatment, and hormonal contraceptives are not advised, according to Canadian pomalidomide labelling.These precise guidelines are not included on the pomalidomide labelling in the US.
Primidone	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.
Retinoic Acid Derivatives	May reduce the progestins' therapeutic impact (Contraceptive). Progesterone serum levels may be reduced by retinoic acid derivatives (Contraceptive). Treatment: Patients using retinoic acid derivatives should utilise two kinds of reliable contraception. Minipills that contain only microdosed progesterone and no oestrogen are regarded as ineffective forms of contraception. Adapalene, Alitretinoin (Topical), Bexarotene (Topical), and Tretinoin are exceptions (Topical).
Rifamycin Derivatives	May lower the level of progestins in the serum (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.
Saquinavir	May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.
St John's Wort	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Take into account using something other than St. John's wort. Failure with contraception is possible. It is advised to use an alternative, nonhormonal method of birth control.
Sugammadex	May lower the level of progestins in the serum (Contraceptive). Treatment: During and for 7 days after having sugammadex, patients receiving any hormonal contraceptive (oral or non-oral) should utilise an additional, non-hormonal method of contraception.
Tetrahydrocannabinol and Cannabidiol	Could lower the blood level of hormonal contraceptives. Management: Due to the potential for tetrahydrocannabinol and cannabidiol to reduce concentrations and effectiveness of hormonal contraceptives, women using hormonal contraceptives should think about including a barrier contraceptive.
Tipranavir	May raise progesterone levels in the blood (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.
Topiramate	May lower the level of progestins in the serum (Contraceptive). Treatment: Inform patients that this combination may result in decreased contraceptive efficacy. Think about including an additional (non-hormonal) type of birth control.
Vitamin K Antagonists (eg, warfarin)	Vitamin K antagonists' ability to prevent clotting may be lessened by progestins (contraceptives). On the other hand, several products have also been observed to have heightened anticoagulant effects. Management: To reduce the risk of thromboembolic diseases, concurrent hormonal contraceptives and coumarin derivatives should be avoided wherever possible. Think about switching to a hormonal-free method of birth control.
Risk Factor X (Avoid combination)
Encorafenib	May lower the level of progestins in the serum (Contraceptive).
Griseofulvin	May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible.
Indium 111 Capromab Pendetide	Antiandrogens may reduce Indium 111 Capromab Pendetide's ability to diagnose.
Ixazomib	May lower the level of progestins in the serum (Contraceptive). More precisely, the serum concentrations of contraceptive progestins may be lowered when ixazomib and dexamethasone are combined. Treatment: Women of reproductive potential should use a nonhormonal barrier contraceptive for the duration of their ixazomib treatment and for 90 days after.
Tranexamic Acid	Tranexamic Acid's thrombogenic impact may be enhanced by progestins (contraceptives).
Ulipristal	Ulipristal's therapeutic effects may be lessened by progestins. Ulipristal may lessen the progestins' therapeutic effects. Avoid progestins within 12 days of quitting ulipristal for uterine fibroids (Canadian indication); avoid progestins within 5 days of stopping ulipristal for emergency contraception (U.S. indication).

 

Monitoring parameters:

Contraception:

• Assessment of pregnancy status
• weight
• BMI 
• evaluate health changes 
• BMD 

Endometrial cancer:

• Examine BMD after prolonged use; breast cancer (in women with a strong family history of breast cancer).

Endometrial hyperplasia, treatment (off-label use):

• Endometrial samples should be taken every three to six months, while the best frequency has not yet been identified.

Menopause:

• Determine the baseline risk for breast cancer and CVD before starting combination hormonal therapy.
• During therapy, Monitor for:
  • age-appropriate breast and pelvic exams
  • blood pressure
  • unscheduled bleeding lasting >6 months for endometrial pathology 
  • serum triglycerides 
  • Thyroid-stimulating hormone 
• Duration of treatment should be evaluated at least annually.

Treatment of paraphilia/ hypersexuality:

• Liver function test 
• CBC 
• serum testosterone 
• serum LH and prolactin
• glucose levels
• bone scan 
• gallbladder function

---

How to administer Medroxyprogesterone acetate (Depo-Provera)?

SubQ:

• Depo-subQ Provera 104:
  • Give the first dose during the first five days of your period, or, if you're breastfeeding, at six weeks after giving birth.
  • Shake ferociously for at least a minute before using.
  • Use a SubQ injection to administer; stay away from the umbilicus and the front of the thigh or abdomen.
  • Give slowly over a period of 5 to 7 seconds. Avoid rubbing the injection site. With each injection, switch the administration location.
  • The initial injection should be given no later than seven days following the last active tablet or removal of the patch or ring when moving from combined hormonal contraceptives (oestrogen + progestin).
  • To guarantee continued coverage when moving from an intramuscular to a subcutaneous formulation, the subsequent dose should be administered during the intramuscular injection's recommended dosing window.

IM, SubQ:

• Additional contraceptive considerations:
  • Once it is determined that the lady is not pregnant, the available recommendations state that the first injection may be administered at any point during the menstrual cycle.
  • If administered within seven days of the start of menstruation, just after delivery, or right after an unplanned or forced abortion, further contraception is not required.
  • Unless the injection is administered during a surgical abortion, further contraception is required for the next seven days.
  • If the injection is administered more than seven days after the onset of menstrual flow, a second method of contraception must be taken for seven days unless the woman abstains from sexual activity.
  • If a woman has had sex since the beginning of her last menstrual cycle and is switching from an IUD to an injection, you may want to postpone the IUD removal for 7 days after the first injection, advise her to use barrier contraception or refrain from sex for 7 days prior to the switch, or you may want to consider emergency contraception at the time of IUD removal.
  • Repeat injections should be given every 13 weeks when using contraception, though they can be administered earlier if necessary.
    Injections can be administered up to two weeks after the scheduled date; however, if it has been more than 15 weeks since the last shot, pregnancy should be checked out and supplementary contraception should be used for 7 days.

---

Mechanism of action of Medroxyprogesterone acetate (Depo-Provera):

• Proliferative endometrium is converted to secretory endometrial by medroxyprogesterone acetate (MPA).
• MPA can be used in conjunction with conjugated estrogens to lower the risk of adenocarcinoma and endometrial hyperplasia (EH).
• MPA can be injected for contraception (doses 150 mg IM and 104 mg SubQ).
• Due to the inhibition of pituitary gonadotropin production, ovulation is lost and follicular maturation occurs.
• Medroxyprogesterone, a progestogen, can cause atrophy of the endometrial tissues when it is used for endometriosis.
• They can also hinder new growth and prevent implantation. Endometriosis can cause pain.

The beginning of action:

• • Time until ovulation (after last injection): 10 Months (range: 6-12 months).

Absorption:

• Oral: Rapid absorbtion;
• Intramascular: Slow absorbtion

Protein binding:

• 86% to 90% primarily to albumin; does not bind to sex hormone-binding globulin

Metabolism:

• Extensively hepatic via hydroxylation and conjugation; forms metabolites

Bioavailability:

• 0.6% to 10%

Half-life elimination:

• Oral: 12 to 17 hours;
• Intramuscular (Depo-Provera Contraceptive): ~50 days;
• SubQ: ~43 days

Time to peak:

• Oral: 2 to 4 hours;
• Intramuscular (Depo-Provera Contraceptive): ~3 weeks;
• SubQ: ~1 week

Excretion:

• Urine

---

International Brand Names of Medroxyprogesterone acetate:

• Depo-Provera
• Depo-SubQ Provera 104
• Provera
• Climanor
• Clinofem
• Condep
• Cycrin
• Depo Progestin
• Depo Provera
• Depo-M
• Depo-Prodasone
• Depo-Provera
• Depo-Ralovera
• Depofemme
• Depomoxie
• Deponeo
• Deporeva
• Depotrust
• Deviry
• Enaf-150
• Farlutal
• GestaPolar
• Gestapuran
• Livomedrox
• Lyndavel
• Manodepo
• Medogen
• Medrina
• Medrone
• Medroxine
• Megestron
• Meprate
• Meterone
• Miprox
• Movera
• MPA Gyn 5
• Non-Preg
• Oxyprogest
• Perlutex
• Petogen
• Prodafem
• Progen
• Progevera
• Provenor
• Provera
• Provera LD
• Ralovera
• Ravimed
• Sayana
• Sayana Press
• Triclovera
• Veraplex

---

Medroxyprogesterone acetate Brand Names in Pakistan:

Medroxyprogesterone Acetate Injection 500 Mg in Pakistan
Medrosterona	Seignior Pharma

 

Medroxyprogesterone Acetate Injection 150 Mg/Ml in Pakistan
Depo Provera Saheli	Pfizer Laboratories Ltd.
Famila	Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Medroxy Depo	Global Pharmaceuticals
Megestron	Social Marketing Pakistan (Guarantee) Ltd.

 

Medroxyprogesterone Acetate Tablets 250 Mg in Pakistan
Ciclotal	Scharper Pharmaceuticals (Pvt) Ltd.

 

Medroxyprogesterone Acetate Tablets 500 Mg in Pakistan
Ciclotal	Scharper Pharmaceuticals (Pvt) Ltd.

 

Medroxyprogesterone Acetate Caps 500 Mg in Pakistan
Medrosterona	Seignior Pharma
Medroxyprogesterone	Medinet Pharmaceuticals